Tyrosine protein kinases play a central role in the regulation of cell multiplication. This project is directed at understanding the function of the tyrosine protein kinase encoded by the lck proto-oncogene, p56lck. This regulatory molecule is of interest because it is expressed exclusively in lymphoid cells and because it is implicated in lymphomagenesis. The work has three parts. One is designed to define precisely the transforming potential of wild-type lck and of genetically-activated lck. This will be done by the infection of neo-natal mice and cultured lymphoid cells with retroviruses expressing p56lck. The identity of transformed cells will be determined by the analysis of surface markers. This should reveal the types of cells that this protein can transform. Additionally, the potential role of p56lck in human leukemia will be examined by characterization of the protein in leukemic cell lines. Second, the role of p56lck in normal lymphoid function will be examined. Agents that induce the dephosphorylation and activation of p56lck will be sought and their mode of action determined. Additionally, the effect of ectopic or excessive expression of p56lck on the function of hematopoietic cell lines will be examined by infection with retroviruses encoding p56lck and determination of the functional properties of the infected cells. From perturbations of function, it is hoped that the normal function of the protein can be inferred. Finally, because lck is expressed only in lymphoid cells, the structure and properties of the promoters and enhancers driving the expression of the gene are of considerable interest. These will be isolated by molecular cloning and the regions conferring specificity will be identified through the use of luciferase as a reporter gene.